The role of scavenger receptor BI in hepatitis - eTheses Repository ...

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1.7.2 Low density lipoprotein receptor and virus entry.
Several reports provide evidence that LDLR may be an additional candidate
receptor for HCV attachment and entry, notably, these studies were carried
out almost exclusively with patient serum derived virus. Low density serum
HCV will bind to cells expressing LDLR, whereas higher density particles do
not (218, 336). This interaction is inhibited by the addition of native LDL,
alternatively removal of cell associated LDL enhances HCV binding (95, 218,
336), these data suggest that HCV interacts with LDLR in an analogous
manner to its natural ligand. A recent study by Molina et. al. demonstrated
that infection of primary human hepatocytes by serum HCV is inhibited by
anti-LDLR mAbs and recombinant soluble LDLR peptides, furthermore,
treatments to modulate LDLR expression similarly affected HCV infection
(216). However, the above observations have yet to be recapitulated using
the HCVcc/pp systems (24), thus limiting our understanding of HCV-LDLR
interactions. Current data suggest that envelope proteins do not interact with
LDLR directly (24, 336) and that HCV relies on associated lipoproteins for
binding (219, 337), it is likely that HCVcc/pp are not sufficiently lipoprotein-like
for this to occur.
As illustrated by investigations on the role of LDLR in HCV entry, in vitro
generated HCVcc may not represent native HCV circulating within an infected
individual. Cultured human hepatoma cells often have restrictions in their
ability to assemble lipid rich VLDL particles (316), this would almost certainly
impact on the nature of secreted HCV LVP. Moreover, circulating lipoproteins
undergo continual modification in response to metabolic requirements (321).